Association of Mitochondrial DNA Copy Number and Telomere Length with Prevalent and Incident Cancer and Cancer Mortality in Women: A Prospective Swedish Population-Based Study.

Abstract

Simple SummaryIndividuals with abnormal alterations in mitochondrial DNA copy number (mtDNA-CN) and telomere length are at higher risk of developing certain types of cancer. This report suggests that mtDNA-CN and relative telomere length measured in peripheral blood have potential clinical applications for risk prediction of different cancers and that mtDNA-CN could be used as a prognostic biomarker in malignancy. This comprehensive work strengthens several previous relevant findings in certain types of cancer and broadens our understanding of the link between mtDNA-CN, telomere length and future risk of many cancer types. The translational implication of our findings is that postmenopausal genital organ cancer patients with lower levels of baseline mtDNA-CN or shorter telomere length can be identified for early adjustment of lifestyle and hormone replacement therapy.Changes in mitochondrial DNA copy number (mtDNA-CN) and telomere length have, separately, been proposed as risk factors for various cancer types. However, those results are conflicting. Here, mtDNA-CN and relative telomere length were measured in 3225 middle-aged women included in a large population-based prospective cohort. The baseline mtDNA-CN in patients with prevalent breast cancer was significantly higher (12.39 copies/µL) than cancer-free individuals. During an average of 15.2 years of follow-up, 520 patients were diagnosed with cancer. Lower mtDNA-CN was associated with decreased risk of genital organ cancer (hazard ratio (HR), 0.84), and shorter telomere length was associated with increased risk of urinary system cancer (HR, 1.79). Furthermore, mtDNA-CN was inversely associated with all-cause (HR, 1.20) and cancer-specific mortality (HR, 1.21) when considering all cancer types. Surprisingly, shorter telomere length was associated with decreased risk of cancer-specific mortality when considering all cancer types (HR, 0.85). Finally, lower mtDNA-CN and shorter telomere length were associated with increased risk of both all-cause and cancer-specific mortality in genital organ cancer patients. In this study population, we found that mtDNA-CN and telomere length were significantly associated with prevalent and incident cancer and cancer mortality. However, these associations were cancer type specific and need further investigation.